ORCID Profile
0000-0002-4793-6290
Current Organisation
University of Bristol
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Publisher: Cold Spring Harbor Laboratory
Date: 18-01-2019
DOI: 10.1101/524769
Abstract: Attention-deficit hyperactivity disorder (ADHD) has consistently been associated with substance (ab)use, but the nature of this association is not fully understood. In view of preventive efforts, a vital question is whether there are causal effects, from ADHD to substance use and/or from substance use to ADHD. We applied bidirectional Mendelian randomization using summary-level data from the largest available genome-wide association studies (GWASs) on ADHD, smoking (initiation, cigarettes/day, cessation, and a compound measure of lifetime smoking), alcohol use (drinks/week and alcohol use disorder), cannabis use (initiation and cannabis use disorder (CUD)) and coffee consumption (cups/day). Genetic variants robustly associated with the ‘exposure’ were selected as instruments and then identified in the ‘outcome’ GWAS. Effect estimates from in idual genetic variants were combined with inverse-variance weighted regression and five sensitivity analyses were applied (weighted median, weighted mode, MR-Egger, generalized summary-data-based MR, and Steiger filtering). We found strong evidence that liability to ADHD increases likelihood of smoking initiation and also cigarettes per day among smokers, decreases likelihood of smoking cessation, and increases likelihood of cannabis initiation and CUD. In the other direction, there was evidence that liability to smoking initiation and CUD increase ADHD risk. There was no clear evidence of causal effects between liability to ADHD and alcohol or caffeine consumption. We find evidence for causal effects of liability to ADHD on smoking and cannabis use, and of liability to smoking and cannabis use on ADHD risk, indicating bidirectional pathways. Further work is needed to explore causal mechanisms.
Publisher: Wiley
Date: 15-11-2022
DOI: 10.1002/AJMG.B.32922
Abstract: Ubiquitous associations have been detected between different types of childhood psychopathology and polygenic risk scores based on adult psychiatric disorders and related adult outcomes, indicating that genetic factors partly explain the association between childhood psychopathology and adult outcomes. However, these analyses in general do not take into account the correlations between the adult trait and disorder polygenic risk scores. This study aimed to further clarify the influence of genetic factors on associations between childhood psychopathology and adult outcomes by accounting for these correlations. Using a multivariate multivariable regression, we analyzed associations of childhood attention‐deficit/hyperactivity disorder (ADHD), internalizing, and social problems, with polygenic scores (PGS) of adult disorders and traits including major depression, bipolar disorder, subjective well‐being, neuroticism, insomnia, educational attainment, and body mass index (BMI), derived for 20,539 children aged 8.5–10.5 years. After correcting for correlations between the adult phenotypes, major depression PGS were associated with all three childhood traits, that is, ADHD, internalizing, and social problems. In addition, BMI PGS were associated with ADHD symptoms and social problems, while neuroticism PGS were only associated with internalizing problems and educational attainment PGS were only associated with ADHD symptoms. PGS of bipolar disorder, subjective well‐being, and insomnia were not associated with any childhood traits. Our findings suggest that associations between childhood psychopathology and adult traits like insomnia and subjective well‐being may be primarily driven by genetic factors that influence adult major depression. Additionally, specific childhood phenotypes are genetically associated with educational attainment, BMI and neuroticism.
Publisher: Cambridge University Press (CUP)
Date: 06-11-2019
DOI: 10.1017/S0033291719002678
Abstract: Smoking prevalence is higher amongst in iduals with schizophrenia and depression compared with the general population. Mendelian randomisation (MR) can examine whether this association is causal using genetic variants identified in genome-wide association studies (GWAS). We conducted two-s le MR to explore the bi-directional effects of smoking on schizophrenia and depression. For smoking behaviour, we used (1) smoking initiation GWAS from the GSCAN consortium and (2) we conducted our own GWAS of lifetime smoking behaviour (which captures smoking duration, heaviness and cessation) in a s le of 462690 in iduals from the UK Biobank. We validated this instrument using positive control outcomes (e.g. lung cancer). For schizophrenia and depression we used GWAS from the PGC consortium. There was strong evidence to suggest smoking is a risk factor for both schizophrenia (odds ratio (OR) 2.27, 95% confidence interval (CI) 1.67–3.08, p 0.001) and depression (OR 1.99, 95% CI 1.71–2.32, p 0.001). Results were consistent across both lifetime smoking and smoking initiation. We found some evidence that genetic liability to depression increases smoking ( β = 0.091, 95% CI 0.027–0.155, p = 0.005) but evidence was mixed for schizophrenia ( β = 0.022, 95% CI 0.005–0.038, p = 0.009) with very weak evidence for an effect on smoking initiation. These findings suggest that the association between smoking, schizophrenia and depression is due, at least in part, to a causal effect of smoking, providing further evidence for the detrimental consequences of smoking on mental health.
Publisher: American Psychiatric Association Publishing
Date: 07-2019
Publisher: Elsevier BV
Date: 07-2022
DOI: 10.1016/J.JAAC.2021.11.035
Abstract: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for s le overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. The meta-analysis of overall internalizing symptoms (INT Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood s les will be key in paving the way to future GWAS success.
Publisher: Cambridge University Press (CUP)
Date: 10-2012
DOI: 10.1017/S0033291712001924
Abstract: Cannabis can induce transient psychotic symptoms, but not all users experience these adverse effects. We compared the neural response to Δ 9 -tetrahydrocannabinol (THC) in healthy volunteers in whom the drug did or did not induce acute psychotic symptoms. In a double-blind, placebo-controlled, pseudorandomized design, 21 healthy men with minimal experience of cannabis were given either 10 mg THC or placebo, orally. Behavioural and functional magnetic resonance imaging measures were then recorded whilst they performed a go/no-go task. The s le was sub ided on the basis of the Positive and Negative Syndrome Scale positive score following administration of THC into transiently psychotic (TP n = 11) and non-psychotic (NP n = 10) groups. During the THC condition, TP subjects made more frequent inhibition errors than the NP group and showed differential activation relative to the NP group in the left parahippoc al gyrus, the left and right middle temporal gyri and in the right cerebellum. In these regions, THC had opposite effects on activation relative to placebo in the two groups. The TP group also showed less activation than the NP group in the right middle temporal gyrus and cerebellum, independent of the effects of THC. In this first demonstration of inter-subject variability in sensitivity to the psychotogenic effects of THC, we found that the presence of acute psychotic symptoms was associated with a differential effect of THC on activation in the ventral and medial temporal cortex and cerebellum, suggesting that these regions mediate the effects of the drug on psychotic symptoms.
Publisher: Springer Science and Business Media LLC
Date: 18-03-2023
DOI: 10.1038/S41398-023-02348-Y
Abstract: Parental genes may indirectly influence offspring psychiatric outcomes through the environment that parents create for their children. These indirect genetic effects, also known as genetic nurture, could explain in idual differences in common internalising and externalising psychiatric symptoms during childhood. Advanced statistical genetic methods leverage data from families to estimate the overall contribution of parental genetic nurture effects. This study included up to 10,499 children, 5990 mother–child pairs, and 6,222 father–child pairs from the Norwegian Mother Father and Child Study. Genome-based restricted maximum likelihood (GREML) models were applied using software packages GCTA and M-GCTA to estimate variance in maternally reported depressive, disruptive, and attention-deficit hyperactivity disorder (ADHD) symptoms in 8-year-olds that was explained by direct offspring genetic effects and maternal or paternal genetic nurture. There was no strong evidence of genetic nurture in this s le, although a suggestive paternal genetic nurture effect on offspring depressive symptoms (variance explained (V) = 0.098, standard error (SE) = 0.057) and a suggestive maternal genetic nurture effect on ADHD symptoms (V = 0.084, SE = 0.058) was observed. The results indicate that parental genetic nurture effects could be of some relevance in explaining in idual differences in childhood psychiatric symptoms. However, robustly estimating their contribution is a challenge for researchers given the current paucity of large-scale s les of genotyped families with information on childhood psychiatric outcomes.
Publisher: Elsevier BV
Date: 2013
DOI: 10.1016/J.PHYSBEH.2012.11.003
Abstract: The aim of this study was to systematically review the literature on obstetric factors at birth and their role as risk factors for a subsequent eating disorder (ED) and where possible to perform a meta-analysis of case-control studies of EDs and obstetric complications (OCs). Studies were ascertained by computer searches of electronic databases (Medline, PsycINFO, Web of Science and CINAHL), searches of reference lists and from raw data obtained upon request from the authors. A total of 14 studies were identified for the systematic review, of which 6 were eligible for the subsequent meta-analysis. Of the selected 6 studies, 5 reported on the same OCs, namely vaginal instrumental delivery and prematurity. Accordingly, meta-analyses were run on these two variables. Both analyses were conducted on anorexia nervosa (AN) patients. Findings from the systematic review were conflicting, with some studies reporting a significant relationship between OCs and ED diagnoses and/or ED symptomatology and others refuting it. A non-significant association of instrumental delivery [pooled odds ratio (OR) 1.06, 95%CI: 0.69, 1.65] and prematurity [pooled OR 1.17, 95%CI: 0.91, 1.52] with AN was revealed in our meta-analysis. The current literature on OCs as risk factors for a later ED is contradictory. The range of different occurrences considered as OCs and methodological limitations hinder ultimate conclusions. Upcoming studies should pool datasets together to obtain sufficient power to assess OCs and EDs in combination.
Publisher: The Royal Society
Date: 03-2019
DOI: 10.1098/RSOS.181049
Abstract: Schizophrenia is a debilitating and heritable mental disorder associated with lower reproductive success. However, the prevalence of schizophrenia is stable over populations and time, resulting in an evolutionary puzzle: how is schizophrenia maintained in the population, given its apparent fitness costs? One possibility is that increased genetic liability for schizophrenia, in the absence of the disorder itself, may confer some reproductive advantage. We assessed the correlation and causal effect of genetic liability for schizophrenia with number of children, age at first birth and number of sexual partners using data from the Psychiatric Genomics Consortium and UK Biobank. Linkage disequilibrium score regression showed little evidence of genetic correlation between genetic liability for schizophrenia and number of children ( r g = 0.002, p = 0.84), age at first birth ( r g = −0.007, p = 0.45) or number of sexual partners ( r g = 0.007, p = 0.42). Mendelian randomization indicated no robust evidence of a causal effect of genetic liability for schizophrenia on number of children (mean difference: 0.003 increase in number of children per doubling in the natural log odds ratio of schizophrenia risk, 95% confidence interval (CI): −0.003 to 0.009, p = 0.39) or age at first birth (−0.004 years lower age at first birth, 95% CI: −0.043 to 0.034, p = 0.82). We find some evidence of a positive effect of genetic liability for schizophrenia on number of sexual partners (0.165 increase in the number of sexual partners, 95% CI: 0.117–0.212, p = 5.30×10 −10 ). These results suggest that increased genetic liability for schizophrenia does not confer a fitness advantage but does increase mating success.
Publisher: American Medical Association (AMA)
Date: 07-2020
Publisher: Springer Science and Business Media LLC
Date: 25-10-2022
DOI: 10.1038/S41380-022-01793-3
Abstract: Despite the substantial heritability of antisocial behavior (ASB), specific genetic variants robustly associated with the trait have not been identified. The present study by the Broad Antisocial Behavior Consortium (BroadABC) meta-analyzed data from 28 discovery s les (N = 85,359) and five independent replication s les (N = 8058) with genotypic data and broad measures of ASB. We identified the first significant genetic associations with broad ASB, involving common intronic variants in the forkhead box protein P2 (FOXP2) gene (lead SNP rs12536335, p = 6.32 × 10
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Hannah Sallis.